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Saturday, September 17, 2016

Multiple Sclerosis, Guillain Barre, and Amyotrophic Lateral Sclerosis (ALS)

Multiple Sclerosis, Guillain-Barre, and ALS commonly appear on exams because of their similarities, but its the subtle differences and keywords you should look out for, especially on physical exam. While historically, the PANCE and PACKRAT are only 6% Neurology questions, these are a few that you shouldn’t miss. Do you know multiple sclerosis as well as you think you do? Would you be able to diagnose and work someone up for ALS if you saw their presentation in an ED? Guillain-Barre has its own special findings on lumbar puncture that you don't want to forget. If it's in your differential and you can rule out things like meningitis, make sure you know the things you'd expect on a lumbar puncture. These are all great points to know, though this is not meant to be an all-inclusive review. You'll definitely want to review multiple sclerosis medications before your exam, including which are first line and which are actually long term (disease modifying) vs. acute treatment. Good luck out there!


I hope this review helps you regardless of which avenue you find it useful. Make sure to check out TrueLearn’s free sample questions below! The vignette style questions are exactly what you need to prepare yourself for EOR, PANCE, PACKRAT, and PANRE-related questions.


Multiple Sclerosis, Guillain Barre, and Amyotrophic Lateral Sclerosis (ALS)
  • Selective demyelination of CNS - multifocal zones of demyelination (plaques) scattered throughout white matter (angles of lateral ventricles)
  • Demyelination - involves white matter of the brain and spinal cord; tends to spare the gray matter/axons and the PNS
  • Internuclear ophthalmoplegia (INO) - lesion in the medial longitudinal fasciculus results in ipsilateral medial rectus palsy on attempted lateral gaze (adduction defect) and horizontal nystagmus of abducting eye (contralateral to side of lesion)
  • Relapses of MS produce symptoms for >24 hours, once per year, decrease in frequency over time
  • Prognosis: variable, normal life spans
    • Most never develop debilitating disease, 1/3 progress to severe disability
    • RF for severe: frequent attacks early in course, onset at old age, progressive course, early cerebellar or pyramidal involvement
  • Disease activity is based on enhancing lesions on MRI or functional symptoms (motor deficits)
  • ‘Silent symptoms’: dementia (cognitive impairment), pain
Multiple Sclerosis
Women (2x) > men
Etiology: unknown

Most present in 20-30s with localizing deficit such as optic neuritis, one-sided weakness, or numbness
1. Transient sensory deficits (most common), decreased sensation or paresthesias in upper or lower limbs
2. Fatigue - most common complaints
3. Motor symptoms: weakness or spasticity (insidious or acute)
--Pyramidal tract involvement (UMN)
--Spasticity (legs) can impair ability to walk and maintain balance
--Leads to weakness → paraparesis, hemiparesis, quadriparesis
4. Visual disturbances
--Optic neuritis (monocular visual loss, pain with movement of eyes, central scotoma, decreased pupillary reaction to light)
--Internuclear ophthalmoplegia (strongly suggests): adduction defect, horizontal nystagmus of abducting eye
5. Cerebellar involvement: ataxia, intention tremor, dysarthria
6. Loss of bladder control - UMN injury
7. Autonomic involvement: impotence or constipation
8. Cerebral involvement: memory loss, personality change, emotional lability (anxiety & depression common)
9. Neuropathic pain: hyperesthesia, trigeminal neuralgia
Diagnosis:
1. Clinical definite
-2 episodes of SX
-Evidence of 2 white matter lesions (imaging or clinical)

2. Lab-supported
-2 episodes of SX
-Evidence of 1 white matter lesion on MRI
-Abnormal CSF (oligoclonal bands)

3. Probable
-2 episodes of SX
+ 1 white matter lesion
OR
+ CSF: oligoclonal bands
Clinically Silent
“Stable” or “benign”
Clinical Diagnosis
MRI - test of choice, most sensitive, diagnostic
--Demyelinating lesions, number does not correlate to severity or speed of progression
LP/CSF Analysis: oligoclonal bands of IgG (90%)
-Not required for relapses, clinical diagnosis
Evoked potentials: slow sensory impulses


Goal: reduce the frequency and severity of recurrent attacks - start beta interferons as early as possible
Acute attacks
1. High dose IV steroids, shorten attack, but does not alter outcome or course, resolves in 6 weeks with or without
-PO Decadron or Prednisone

Disease Modifying
1. Recombinant Interferon B-1a/1b and glatiramer acetate (first line treatment)  
a. Can cause flu-like symptoms, but reduce relapse rates
b. Cyclophosphamide for rapidly progressive, but toxic

Symptomatic Therapy
a. Baclofen or dantrolene for spasticity
b. Carbamazepine or gabapentin for neuropathic pain
c. Treat depression
Relapsing and Remitting (R&R)
Most common: exacerbations with remissions
Secondary Progressive
R&R disease with gradual worsening of SX that is progressive in later years
Primary Progressive
Steady progressive disease that appears later in life (>40), less visual and more axonal involvement
NMO (Neuromyelitis Optica, Devic Disease)
Etiology: unknown

Primarily mediated by the humoral immune system

F>M, age 32-41
1. Acute attacks of bilateral or rapidly sequential optic neuritis
-Severe visual loss
-Transverse myelitis (limb weakness, sensory loss, bladder dysfunction)
-Occurs over days
2. Intractable nausea, vomiting, hiccups
3. Daytime somnolence or narcolepsy
4. Pain in the trunk and legs (80%)

Complications: Reversible posterior leukoencephalopathy, neuroendocrine disorders, seizures  
1. Aquaporin-4 autoanitbody (NMO IgG antibody): confirms dx
-Mod sens, highly specific
2. Brain and SC MRI: longitudinal extensive SC lesions on T2  (3+ vertebral segments involving gray matter), “owl-eye” sign
-Enhancement of the optic nerves
3. LP
-Pleocytosis
-High protein levels
-Absent oligoclonal bands
1. HD IV steroids → PLEX
2. Long term
90% have relapsing course

Prevention
1. Long term immunosuppression
-AZA, Mycophenolate mofetil, Rituximab, Methotrexate, Mitoxantrone, oral steroids
Guillain-Barre Syndrome (ascending polyneuropathy with areflexia)
Autoimmune reaction against peripheral nerves

Inflammatory demyelinating polyneuropathy affecting motor nerves

Circulating antibodies against the postsynaptic nicotinic acetylcholine receptors at the NMJ of skeletal muscle cells

Bimodal: 20-30 (women), 60-70 (men)

HX: previous viral infection (C. jejuni, CMV, hepatitis, HIV), surgery, or vaccination

1. Abrupt onset
2. Rapidly progressive bilateral weakness
-Becomes more severe with repeated use of or during course of day
-Loss of sensation in “stocking-glove” distribution of all 4 extremities
-Usually symmetric
-Progresses from distal to central muscles
-Mild or severe
3. Sphincter control and micturition spared
-Autonomic features: arrhythmias, tachycardia, postural hypotension
Lumbar puncture
-Increased protein
-NL glucose, pressure

Electrodiagnostics: decreased motor nerve conduction velocity
1. Admit & monitor for respiratory failure
2. Plasmapheresis (IVIG) for severe respiratory compromise or weakness

DO NOT GIVE STEROIDS → harmful
Amyotrophic Lateral Sclerosis (Lou Gehrig’s Disease)
Amyotrophy with the pathological finding of lateral sclerosis
65-70: men > women
peak: 70-80s, but can occur in 20’s

Sporadic
Only 10% familial
1. Asymmetric limb weakness (80%) -
-Upper extremity onset: hand weakness, but may begin in shoulder girdle
-Lower extremity: weakness of foot dorsiflexion (foot drop)
2. Bulbar symptoms: dysarthria, dysphagia
-Coughing, choking
-Increased masseter tone and difficulty opening mouth (trismus)
-Laryngospasm
3. Autonomic symptoms: constipation, urgency without incontinence, excessive sweating
-Early satiety, bloating
4. Parkinsonism and supranuclear gaze palsy
-Facial masking, tremor, bradykinesia, postural instability
5. Sensory (20-30%): tingling
4. Respiratory: muscle weakness, generalized weakness
5. Weight loss
DX: Clinical
1. Upper and Lower MN signs and symptoms
2. Progressive spread

EMG: fibrillations, positive sharp waves
Electrodiagnostics: decreased motor conduction velocity
MRI (preferred) to r/o other causes

Unilateral arm onset (MC) → contralateral arm → ipsilateral leg → contralateral leg → bulbar muscles

Unilateral leg → contralateral leg → ipsilateral arm → contralateral arm → bulbar muscles
1. Riluzole 50 mg BID
AE: asthenia, dizziness, GI upset, elevated LFTs



MCC death: progressive respiratory failure

Complications: aspiration

Median survival: 3-5 years


True Learn Questions
Question 1: You are consulted to see a 46 year-old female who has developed rapidly-progressing weakness with decreased sensation in her upper and lower distal extremities bilaterally in a “stocking-glove” distribution. Further questioning reveals the patient has just recovered from an upper respiratory tract infection. Based on this information, lumbar puncture would most likely show:
  1. Increased protein, increased pressure, and decreased glucose
  2. Decreased protein, increased pressure, and increased glucose
  3. Decreased protein, decreased pressure, and normal glucose
  4. Increased protein, normal pressure, and decreased glucose
  5. Increased protein, normal pressure, and normal glucose


Explanation:
This is a classic presentation of Guillain-Barre syndrome, which is manifested by rapidly-progressive bilateral weakness and loss of sensation in a “stocking-glove” distribution. Guillain-Barre syndrome is commonly seen following viral infections and occasionally in patients after undergoing surgery or vaccination. Lumbar puncture would likely reveal increased protein with normal pressure and glucose. Incorrect: Answer (A): This CSF profile is inconsistent with that seen Guillain-Barre syndrome. This profile may be seen in patients with meningitis. Incorrect: Answers (B, C & D): This CSF profile is inconsistent with that seen Guillain-Barre syndrome. Bottom Line: Lumbar puncture performed in patients with Guillain-Barre syndrome typically shows increased protein with normal pressure and glucose.


Question 2: A 20-year-old college student presents with weakness in his right leg following exercise and increased fatigue. He noticed the changes in his leg when he was running and has tripped over his right foot several times. He denies headache, pain in the affected limb, sensory changes, visual disturbance, or loss of balance. When asked, he says that he feels most tired after exercising or taking a hot shower. On examination, strength is 5/5 except for right ankle flexors, which are 4/5. Sensation is intact globally. Reflexes are 2+ globally except for right ankle jerk, which is 3+. Babinski is present on the right. Cerebrospinal fluid (CSF) has oligoclonal bands and an elevated IgG index. CSF fluorescent Treponemal antibody is negative. Glucose and cell count are normal. Which of the following would be expected on brain MRI?
  1. Contrast non-enhancing mass lesion
  2. Multiple ring enhancing lesions
  3. Multiple white matter hyperintensities
  4. Ring-enhancing parenchymal mass lesion
  5. T1 hypointensities


Explanation:
This patient is presenting with symptoms suggestive of multiple sclerosis. Patients can present with a variety of neurologic complaints. This patient notes weakness in his right leg and a foot drop. He also has hyperreflexia in the right ankle. The diagnosis of multiple sclerosis is confirmed by oligoclonal bands in the CSF and an elevated IgG index. Multiple sclerosis causes multiple white matter hyperintensities to be seen on an MRI.


Answer A: A contrast non-enhancing mass lesion would be seen in the event of a low-grade oligodendroglioma or similar benign neoplastic lesion.
Answer B: Multiple ring-enhancing lesions would be seen with toxoplasmosis.
Answer D: A ring-enhancing mass lesion would be seen with a malignant neoplastic lesion, such as glioblastoma multiforme.
Answer E: T1 hypointensities are seen in multiple sclerosis late in the course of the disease. Multiple areas of hyperintensity in the white matter is more likely at this stage of the patient's disease.
Bottom Line: CSF findings in multiple sclerosis include oligoclonal bands and an elevated IgG index. Multiple white matter hyperintensities are seen on a brain MRI.


Question 3: A 55 year-old man presents to your office complaining of muscle weakness, twitching and loss of definition in the muscles in his hands. He denies sensory disturbances and bowel or bladder problems. He is diagnosed with a disease of both upper and lower motor neurons. What is the preferred treatment for his condition?
  1. Observation and reassurance
  2. Glutamate antagonist
  3. Glutamate agonist
  4. Dopamine agonist
  5. Dopamine antagonist


Explanation:
The most likely diagnosis in this patient is amyotrophic lateral sclerosis. ALS, also known as Lou Gehrig’s disease, is a degenerative disease affecting both upper and lower motor neurons. It usually presents in males between the ages of 40-60. Most cases are sporadic, however familial cases involve mutations in the superoxide dismutase gene on chromosome 21. Clinical findings include those of upper motor neuron disease such as spasticity and Babinksi’s sign. Lower motor neuron findings include muscle weakness which usually begins with atrophy of the intrinsic muscles of the hand. Eventually lower motor neurons to the diaphragm are affected and the patient becomes ventilator dependent. ALS only affects motor neurons, therefore sensation, bowel and bladder function is not affected. The only effective treatment involves using a glutamate antagonist such as riluzole. The average survival time after diagnosis is 3-5 years. Riluzole can add up to a year of survival time. Incorrect: Answer (A): Observation and reassurance is not a preferred treatment. Using a glutamate antagonist such as riluzole may add up to a year to the patient's expected survival time. Incorrect: Answer (C): Treatment with a glutamate agonist will likely make the condition worse. Nerve damage is thought to stem from glutamate induced toxicity. Glutamate antagonists are the preferred treatment for ALS. Incorrect: Answer (D): Dopamine agonists are not used in the treatment of ALS. Dopamine agonists may be used in the treatment of Parkinson’s disease. Incorrect: Answer (E): Dopamine antagonists are not used in the treatment of ALS. They can be used in the treatment of diseases where dopamine blockade is beneficial such as schizophrenia. Bottom Line: Glutamate antagonists such as riluzole may be used in the treatment of ALS


3 comments:

  1. Hi Paul,

    I work at a PA Program in California. Is there an email address of phone number I can contact you at? My program director is interested in speaking with you! Thanks so much and have a great day.

    ReplyDelete
    Replies
    1. Hey Natalie,

      Sorry for the delayed response, but I think I already got in contact with her. Thanks for reaching out. I was studying intensely for my PANCE and needed time away from the blog.

      Delete